NCT05003895

GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

Phase I Study of GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: A new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain types of cancer. Objective: To see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe. Eligibility: Adults aged 18 years and older who have Glypican-3 (GPC3) positive solid tumor malignancy. Design: Participants will be screened with the following: Blood and urine tests Medical history Physical exam Heart function tests Review of their symptoms and their ability to perform their normal activities Tumor biopsy Imaging scan of the chest, abdomen, and pelvis Participants will have leukapheresis. They may have an IV (intravenous catheter, a small tube put into an arm vein) inserted into each arm or get a central line. Blood will be removed. A machine will separate the white blood cells from their blood. The rest of their blood will be returned to them. Participants will be admitted to the hospital for about 2 weeks. They will get the chemotherapy drugs fludarabine and cyclophosphamide by IV for 3 days. Then they will receive the modified white blood cells by IV. Participants will have frequent blood draws. They will give blood and tumor samples for research. Participants will have follow-up visits for the next 15 years. Then they will be contacted by email or phone for the rest of their life. If their disease does not get worse after 5 years, they will continue to be invited to do imaging studies every 6 months.

Detailed description

Background: * Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-associated mortality with an average life expectancy of 6-9 months * Despite the success of several studies showing efficacy in treating HCC, most clinical trials have failed to prove a survival advantage. * Adoptive T-cell therapy exploits the natural ability of T-cells to recognize and eliminate their target. * GPC3 is a cell surface protein that is expressed in nearly all HCC yet is undetectable in normal adult hepatic tissues. * GPC3 is also expressed strongly in some non-HCC solid tumor malignancies. * We want to evaluate the role of GPC3 targeted chimeric antigen receptor (CAR)-T cells in advanced GPC3 expressing HCC as well as other advanced solid tumor malignancies with GPC3 expression. Objective: -To determine the safety and feasibility of T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor, in participants with advanced solid tumor malignancy, expressing GPC3. Eligibility: * Histologically confirmed diagnosis of hepatocellular carcinoma or other solid tumor malignancy. * GPC3 positivity of \>= 25% by immunohistochemistry * At least 1 measurable lesion by RECIST v 1.1 criteria * Age \>= 18 years Design: * We plan to conduct a phase I dose escalation designed clinical trial using CAR (hYP7)-T cells in participants with advanced hepatocellular carcinoma or other advanced solid tumor malignancy, expressing GPC3. * Participants will undergo leukapheresis * Participants will receive a lymphocyte depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused CAR-expressing T cells * Following the T cell infusion, there is a mandatory 9-day inpatient hospitalization to monitor for toxicity. * The participants will be closely monitored during the first year after cell infusion and followed for life.

Conditions

• Hepatocellular Carcinoma
• Hepatocellular Cancer
• Metastatic Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Daily x 3 doses on Day -3, -2, -1 300 mg/m2 IV infusion (200 mg/m\^2 in Dose Level -1)
BIOLOGICAL	CAR-T cell	Single infusion on Day 0
DRUG	Fludarabine	Daily x 2 doses on Day -2 and -1 30 mg/m\^2 IV infusion administered following cyclophosphamide

Timeline

• Start date: 2021-12-08
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2021-08-13
• Last updated: 2026-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study